The retinal pigment epithelial (rpe) cell is a major regulatory cell in the eye. That is, the rpe cell exerts a variety of actions in maintaining retinal integrity and function. In order to more effectively study this cell in vivo and in vitro, we have produced monoclonal antibodies directed against human rpe cells. Using immunoperoxidase assays (ABC), we have identified two mouse IgG monoclonal antibodies which react with the human rpe cell. The monoclonal antibodies are both specific for the rpe cell within the eye, since they do not react with any other ocular structures. Moreover, these antibodies do not cross react with human skin, kidney or peripheral mononuclear cells. These antibodies recognize cell surface molecules which are highly conserved since they can be found in man, monkey, rat, mouse, cow, chicken and frog. These are the first monoclonal antibodies which are directed solely at the human rpe cell. Further characterization and studies with this antibody should prove useful in the identification of rpe cells in situ and in vitro. Moreover, this immunoglobulin will allow us to probe the bioregulatory functions of the cell.